Work on Body Design Of Fruit Fly Wins Nobel

By LAWRENCE K. ALTMAN

Published: October 10, 1995

Correction Appended

TWO Americans and a German won the Nobel Prize in Physiology or Medicine yesterday for discovering how genes control the early structural development of the body. The research, which was done in fruit flies, helps to explain birth defects in humans.

The American winners are Dr. Edward B. Lewis, 77, of the California Institute of Technology in Pasadena, Calif., and Dr. Eric F. Wieschaus, 48, of Princeton University. The German is Dr. Christiane Nusslein-Volhard, 52, director of developmental biology at the Max Planck Institute in Tubingen. The three were selected to share the $1 million award by a committee from the Karolinska Institute in Stockholm, which made the announcement.

All three studied the fruit fly, Drosophila, a household nuisance but a time-honored biology tool, to begin to unravel the secrets of how embryos develop from a single cell into well-differentiated anatomical structures like brains and legs. Other researchers have determined that what the three Nobel laureates found in fruit flies also applies to higher species, including humans.

"Together, these three scientists have achieved a breakthrough that will help explain congenital malformations in man," the Nobel committee said in its announcement. "It is likely that mutations in such important genes are responsible for some of the early, spontaneous abortions that occur in man, and for some of the about 40 percent of the congenital malformations that develop due to unknown reasons."

For example, the committee said that very high amounts of vitamin A during early pregnancy are known to disturb genes of the type that the scientists studied to cause severe birth defects.

Mutations in genes related to those in fruit flies have been found to cause human disorders like complete loss of the iris in the eye and a condition known as Waardenburg syndrome, which is characterized by deafness, defects in the facial bones and altered pigmentation of the iris.

Dr. Lewis has said that as a high school student in the 1930's in Wilkes-Barre, Pa., he first became fascinated with natural mutations in fruit flies that produced extra pairs of wings and other anomalies. He went on to earn degrees in biostatistics at the University of Minnesota and genetics and meteorology in Pasadena. In his work, Dr. Lewis laid the foundation for most of what is now known about the genes that regulate the development of specific regions of the body, the Nobel committee said.

Dr. Nusslein-Volhard and Dr. Wieschaus worked together for several years in Heidelberg, Germany, beginning in the late 1970's as they embarked on their scientific careers. Dr. Wieschaus said in an interview that he had become "hooked on fly embryos" as an undergraduate at Yale University and marveled at "how cells in one region of an embryo know how to make a head, how others know to make muscles."

"It was a brave decision by two young scientists at the beginning of their scientific careers," the Nobel committee said. "Nobody before had done anything similar and the chances of success were very uncertain," in part because "the number of genes involved might be very great."

At a news conference at Princeton yesterday, Dr. Wieschaus said, "We were young and foolish, and it was worth trying," although he acknowledged that his team had encountered many setbacks.

Dr. Lewis, a pioneer in genetic research, has said that his work, and what followed, opened up a completely new approach to the study of development and led to a realization that in most animals, and presumably in plants as well, development is controlled by a set of master regulatory genes. Most such genes have important functions during the early growth of the human embryo.

A fertilized egg is spherical, dividing rapidly to form two, four, eight cells and so on. Until the 16-cell stage, the early embryo is symmetrical and all cells are equal. But then cells begin to specialize, and within a week it becomes clear what will form the head and other regions.

The three laureates set out to answer questions about what controls such development. They chose the fruit fly because it develops so fast -- from fertilized egg to embryo within nine days -- and because its genetic structure is similar to that of humans.

They discovered the existence of suites of genes that build up the architecture of a full functioning organism in a series of delicate biochemical maneuvers.

One of the first genes, called "gap," imposes a head-to-tail orientation on the embryo. Then genes called "pair rule" and "even skipped" are deployed to divide the embryo into segments. A third suite of genes called "segment polarity" genes tell each segment which end is which, head or tail.

Once this basic framework for a body plan has been laid down, other genes direct the development of the appropriate organs for each segment, whether wings, legs or antennae.

It was Thomas Hunt Morgan, an early Nobel Prize winner, who found the first Drosophila mutation in 1910. Scientists apparently did not deliberately make mutations until they used X-rays in the 1930's and chemicals in later years. And in the early days of such research, they studied inheritance rather than development.

Correction: October 12, 1995, Thursday An article in Science Times on Tuesday about the awarding of the Nobel Prize in Physiology or Medicine to three scientists, including Dr. Eric F. Wieschaus, misidentified the university where he was an undergraduate. It was Notre Dame, not Yale. (He did graduate study at Yale.)